Pharmaceutical Technology - May 2018

Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing

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12 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m offers the potential of granted patents on the com- position of matter or the means to overcome the suboptimal performance of the original reference product, according to Sleep. Natural and engineerd albumins Human albumin, an abundant natural protein, is a single non-glycosylated polypeptide chain that performs a number of important functions, in- cluding maintaining oncotic pressure, transport, and distribution of a variety of endogenous and exogenous ligands, Sleep says. Its long circulatory half-life of 19 days is due to its interaction with the neonatal Fc receptor (FcRn), which salvages albumin from degradation, and its size. "Biobetter drug developers have exploited albu- min's properties by joining or associating known biological drugs to albumin to extend the circula- tory half-life," he states. "The ability to modify the interaction of albumin with FcRn through selective protein engineering at a few carefully selected positions in albumin, resulting in either an increase or decrease of al- bumin's affinity for FcRn and so allowing tailor- ing of the half-life of drugs by attaching them to the engineered albumins, is a distinct advantage to the developers of biobetter drugs. Albumin is emerging as an extremely versatile and effective delivery tool in drug delivery, particularly in can- cer therapy," Sleep emphasizes (4). The use of engineered albumins, such as Al- bumedix's Veltis platform, in the development of biobetters has opened up opportunities to further extend the time between doses and/or reduce the dose size. In doing so, adverse reactions, which may have been present in the original reference product, would be reduced. "Together, these fac- tors are expected to improve the therapeutic index of Veltis-enabled biobetters," Sleep observes. Further applications Another application of albumin or engineered al- bumins that is being explored in the development of biobetter drugs is for platform purification purposes. "In most cases, the drug, be it a small molecule, peptide, or protein, will be considerably smaller than albumin, and so, to the advantage of the biobetter drug developer, the biochemical and biophysical properties of the albumin-enabled bio- better will be dominated by those of the albumin component," Sleep says. "The availability of a range of albumin-specific affinity matrices, for example, the AlbuPure ma- trix developed by ProMetic BioSciences Ltd in part- nership with Albumedix, which is a highly stable, robust, and non-toxic matrix with high-binding capacity, recovery, and selectivity for human and animal albumins, has allowed the development of platform purification systems. This allows for the effective use of albumin as a purification tag for the drug contained within the biobetter," he adds. Albumin, though a well-known molecule, is still being explored for its significant benefits and growing importance in the development of biobet- ters. Through conjugation and fusion to albumin and engineered albumins, drug developers are able to optimize drug dosing and enable better thera- pies for patients. References 1. Albumin,, accessed April 11, 2018. 2. W. Strohl, BioDrugs 29 (4), 215-239 (2015). 3. D. Sleep "Recombinant Human Albumin: An Effective Ap- proach for Stabilization of Hard-to-Formulate Biopharmaceuti- cals," PEGS (Boston) Conference, April 29, 2016. 4. D. Sleep, Expert Opin. Drug Deliv. 12 (5) 793-812 (2014). PT Developing Technologies

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